Amyloid β oligomerization is induced by brain lipid rafts
Article first published online: 23 MAY 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 99, Issue 3, pages 878–889, 15 October 2006
How to Cite
Kim, S.-I., Yi, J.-S. and Ko, Y.-G. (2006), Amyloid β oligomerization is induced by brain lipid rafts. J. Cell. Biochem., 99: 878–889. doi: 10.1002/jcb.20978
- Issue published online: 25 SEP 2006
- Article first published online: 23 MAY 2006
- Manuscript Accepted: 31 MAR 2006
- Manuscript Received: 10 JAN 2006
- Korea Research Foundation. Grant Number: C00074
- amyloid β;
- lipid rafts;
Detergent-resistant lipid rafts are required for the generation of Aβ as they concentrate not only amyloid precursor protein (APP), but also the β- and γ-secretase that convert APP to Aβ. Recently, Aβ has been shown to be oligomerized, which results in neuronal cytotoxicity and synaptic failure. In this study, we have demonstrated that Aβ oligomers appeared immediately after the incubation of Aβ with lipid rafts isolated from the brain tissues of rats, and were converted into few Aβ fibrils, even after longer periods of incubation. The oligomerization of Aβ was not abolished after the brain lipid rafts were treated with heat, or with protease K, implying that the lipid raft proteins were determined not to be prerequisites for Aβ oligomerization. The cholesterol present in the lipid rafts might not be essential to Aβ oligomerization because Aβ oligomerization was not prevented after the cholesterol was removed from the lipid rafts with methyl-β-cyclodextrin (MβCD). The Aβ oligomerization was accelerated by the application of lipid rafts isolated from ganglioside-rich cells, C2C12 cells, whereas this was not observed with the lipid rafts isolated from ganglioside-poor cells SK-N-MC and HeLa cells. In addition, lipid raft-induced Aβ oligomerization was shown to be inhibited in CHO-K1 cells which were defective with regard to ganglioside biosynthesis. This indicates that Aβ oligomerization requires gangliosides that are enriched in the lipid rafts. J. Cell. Biochem. 99: 878–889, 2006. © 2006 Wiley-Liss, Inc.